title: Exserohilum infections associated with contaminated steroid injections: a clinicopathologic review of 40 cases.
abstract: September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intra-articular injections. Contamination of methylprednisolone acetate with the black mold, Exserohilum rostratum, was the primary cause of the outbreak, with >13,000 persons exposed to the potentially contaminated drug, 741 confirmed drug-related infections, and 55 deaths. Fatal meningitis and localized epidural, paraspinal, and peripheral joint infections occurred. Tissues from 40 laboratory-confirmed cases representing these various clinical entities were evaluated by histopathological analysis, special stains, and IHC to characterize the pathological features and investigate the pathogenesis of infection, and to evaluate methods for detection of Exserohilum in formalin-fixed, paraffin-embedded (FFPE) tissues. Fatal cases had necrosuppurative to granulomatous meningitis and vasculitis, with thrombi and abundant angioinvasive fungi, with extensive involvement of the basilar arterial circulation of the brain. IHC was a highly sensitive method for detection of fungus in FFPE tissues, demonstrating both hyphal forms and granular fungal antigens, and PCR identified Exserohilum in FFPE and fresh tissues. Our findings suggest a pathogenesis for meningitis involving fungal penetration into the cerebrospinal fluid at the injection site, with transport through cerebrospinal fluid to the basal cisterns and subsequent invasion of the basilar arteries. Further studies are needed to characterize Exserohilum and investigate the potential effects of underlying host factors and steroid administration on the pathogenesis of infection.
authors.affiliation: Infectious Diseases Pathology Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. jritter@cdc.gov
authors.forename: Jana M
authors.initials: JM
authors.lastname: Ritter
authors.forename: Atis
authors.initials: A
authors.lastname: Muehlenbachs
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Blau
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Paddock
authors.forename: Wun-Ju
authors.initials: WJ
authors.lastname: Shieh
authors.forename: Clifton P
authors.initials: CP
authors.lastname: Drew
authors.forename: Brigid C
authors.initials: BC
authors.lastname: Batten
authors.forename: Jeanine H
authors.initials: JH
authors.lastname: Bartlett
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Metcalfe
authors.forename: Cau D
authors.initials: CD
authors.lastname: Pham
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
authors.forename: Mitesh
authors.initials: M
authors.lastname: Patel
authors.forename: Lindy
authors.initials: L
authors.lastname: Liu
authors.forename: Tara L
authors.initials: TL
authors.lastname: Jones
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Greer
authors.forename: Jeltley L
authors.initials: JL
authors.lastname: Montague
authors.forename: Elizabeth
authors.initials: E
authors.lastname: White
authors.forename: Dominique C
authors.initials: DC
authors.lastname: Rollin
authors.forename: Cynthia
authors.initials: C
authors.lastname: Seales
authors.forename: Donna
authors.initials: D
authors.lastname: Stewart
authors.forename: Mark V
authors.initials: MV
authors.lastname: Deming
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brandt
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001203:Ascomycota / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D004340:Drug Contamination; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007268:Injections, Epidural; D008297:Male; D008581:Meningitis / Q000382:microbiology / Q000473:pathology; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077555:Methylprednisolone Acetate; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology / Q000209:etiology* / Q000382:microbiology / Q000473:pathology*; D016133:Polymerase Chain Reaction; D013256:Steroids / Q000008:administration & dosage* / Q000009:adverse effects; D014481:United States / Q000453:epidemiology
chemical_list: D013256:Steroids; D000077555:Methylprednisolone Acetate; D008775:Methylprednisolone